Localized resection for colon cancer

Surgical Oncology (2009) 18, 334e342 available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/suronc

REVIEW

Localized resection for colon cancer R.A. Cahill*, J. Leroy, J. Marescaux Department of Surgery, IRCAD/EITS, 1 Place de l’Hopital, Strasbourg 67091, France Accepted 20 August 2008

KEYWORDS Localized resection; Endoscopic resection; Early stage colon cancer; Sentinel node mapping; Natural Orifice Transluminal Endoscopic Surgery (N.O.T.E.S.)

Abstract Localized resection of early stage colon cancer is increasingly technically feasible by truly minimally invasive means. Such techniques as endoscopic submucosal dissection (ESD) and Natural Orifice Transluminal Endoscopic Surgery (N.O.T.E.S.) now raise the prospect of focused intraluminal and transmural resection of small primary tumors without abdominal wall transgression. The potential clinical benefit that patients may accrue from targeted dissection as definitive treatment in place of radical operation is not yet definitively proven but may be considerable at least in the short-term. However, oncological propriety and outcomes must be maintained. In particular methods by which regional nodal staging can be assured if standard operation is avoided need still to be established. Sentinel node mapping is one such putative means of doing so that deserves serious consideration from this perspective as it performs a similar function for breast cancer and melanoma and because there is already considerable evidence to suggest the technique in colonic neoplasia may be at its most accurate in germinal disease. In addition, it may already be employed by laparoscopy while solely transluminal means of its deployment are advancing. While the confluence of operative technologies and techniques now coming on-stream has the potential to precipitate a dramatic shift in the paradigm for the management of early stage colonic neoplasia, considerable confirmatory study is required to ensure that oncology propriety and treatment efficacy is maintained so that patient benefit may be maximized. ª 2008 Elsevier Ltd. All rights reserved.

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 Rationale for standard operative extent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 Appeal of localized resection for colon cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 Specific evidence regarding limited colonic operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 * Corresponding author. Tel.: +353872886417. E-mail addresses: [email protected], [email protected] (R.A. Cahill). 0960-7404/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2008.08.004

Localized resection for colon cancer

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Current means of regional staging colonic cancer without complete mesenteric resection . . . . . . . . . . . . . . . . . 337 Sentinel node mapping for minimally invasive staging of early stage disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 Concluding discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340

Introduction While the benefits of minimized visceral and lymph basin resection are readily apparent for patients with early cancers of the breast, integument, stomach and, even, rectum, the current paradigm for the elective treatment of colon cancer depends on anatomic excision of a long segment of colon with en bloc mesenteric resection in every case. Indeed many experts have already stated their assumption that limiting operative extent in the context of conventional surgical approaches for this disease provides negligible gain [1]. However the attendant short-term morbidity rates are in order of 15e25% depending on whether the operation is performed by an open or laparoscopic approach respectively [2]. Furthermore, there is increasing awareness of additional iatrogenic complications of long-term impact such as sexual and urinary dysfunction that may be associated with extensive dissection [3]. Finally, the high arterial-tie necessary to glean the apical or para-aortic nodes mandates wide intestinal resection to ensure adequate anastomotic vascularization. This predisposes to impaired postoperative bowel function (at least in the short-term) and may contribute to the risk of anastomotic dehiscence. While very understandable in the context of advanced disease, such adverse outcomes are less forgivable in patients with early, truly node negative disease. These patients could have their disease cured by localized resection and only gain reassurance from the mesenteric component of their surgery rather than any therapeutic advantage. As the number of patients presenting with germinal neoplasia is expanding due to increased patient and physician awareness as well as population screening, the clinical advantages and optimum means of application of truly minimally invasive techniques in their address therefore needs serious consideration. Innovative procedures such as endoscopic submucosal dissection (ESD) and laparoscopic-assisted polypectomy now confer the facility to ensure margin-free resection of small primary lesions without conventional operation [4e 7], Furthermore, Natural Orifice Transluminal Endoscopic Surgery (N.O.T.E.S.) portends the prospect of performing narrow-margin transmural resection of such lesions without incurring abdominal wall transgression [8,9], and already hybrid techniques based on this approach are entering the clinical domain [10,11], As much as technical capacity, these techniques however also need to provide a means of consistently ensuring their oncological propriety. Despite advances in gene profiling, biopsy analysis and perioperative imaging, no surrogate measure has yet proven 100% reliable [12]. It therefore remains mandatory at present to ensure that all those with nodal dissemination are detected

so that such patients are not sub-optimally treated [13]. This principle is perhaps especially true in those with early T-stage disease as approximately 10% of even T1 tumors have nodal metastases [14]. An accurate way of precisely determining nodal status without recourse to radical resection is therefore essential for the evolution of true minimally invasive techniques as a compelling alternative to conventional operation. In addition to both improving the efficacy (by determining those with apparently early disease who are in fact unsuitable for localized resection because of nodal dissemination) and expanding the application (by identifying those who are actually node negative despite more advanced mural disease) of endoscopic approaches, a capacity to ensure precise nodal staging without mesenteric excision would allow novel procedures such as N.O.T.E.S. techniques to evolve with a pure focus on the primary lesion. Lymphatic mapping and sentinel node biopsy, if performed by minimally invasive means, may provide the opportunity to assure appropriate patient selection as it does for cancers at other sites. However, the evolution of this technique, at least from this perspective, has been constrained by the use of conventional operation to resect the primary disease. The advance of endoscopic resective techniques means that this may no longer be the case and so the purpose of lymphatic mapping in colon cancer needs re-evaluation [15]. The aim of this review is, first, to discuss the rationale for the conventional surgical approach for colon cancer along with its inherent potential for iatrogenic injury. It will then deliberate the theoretical advantages of limiting operative dissection and analyze the available clinical evidence in support of such a strategy. Finally, it will consider the evidence regarding sentinel node mapping as a means by which oncological providence may be preserved in the absence of en bloc mesenteric dissection. As much as frame the case for minimized dissection, such a review should clearly identify the specific research still necessary to be performed before novel strategies should be proffered in clinical practice.

Rationale for standard operative extent The primary purpose for proposing and performing conventional radical operation for early stage colon cancer is to ensure accurate regional staging. Although radiological imaging can out-rule gross adjacent organ invasion and methods such as endoscopic ultrasound can provide the capacity to accurately stage the degree of mural penetration, to date, no means other than direct analysis has proven wholly convincing for the accurate detection of nodal deposits (see Current means of regional staging

336 colonic cancer without complete mesenteric resection below). Because the location of the first order nodes is not always adjacent to the primary site, adequate oncological staging requires examination of all the regional nodes. Thus the extent of the standard ‘radical’ operation for colonic cancer is determined by the necessity to ensure full lymph node basin clearance concomitantly with resection of the primary in every case (i.e. ‘‘en bloc’’ or radical mesenteric resection) [16]. Although marginal clearance of the primary is usually possible with longitudinal margins between 5 cm and 10 cm (colonic tumors in fact rarely infiltrate more then 2 cm beyond the area of gross involvement [17] and extended margins do not improve oncological outcome [18e20]), the associated radical lymphadenectomy often mandates a larger visceral resection. This is because lymphatic drainage follows the arterial regional blood supply and so proximal vascular ligation (a ‘‘high-tie’’) is necessary to ensure complete resection of the entire lymphatic delta. This manoeuvre is therefore the primary determinant of the extent of the segmental bowel resection required so that the risk of ischemia of the residual bowel and re-anastomosis is minimized. Although there is likely to be a therapeutic value in resecting nodes positive for metastatic disease in colon cancer, the main value of such clearance for truly lymph node negative patients can only be the gain of reassurance. If node negativity could be assured without recourse to standard en bloc resection, the operative extent could clearly be lessened. Furthermore, it is worth considering that formal lymphadenectomy has its limitations even as the ‘gold standard’ method of for staging. Firstly, there is controversy in pathological reporting as to what actually constitutes a ‘lymph node metastases’ with some staging classifications counting the presence of a tumor deposit over a certain size as being ‘nodal’ disease whether or not there is histological evidence of a lymphatic tissue present [77]. Current criteria are in addition based solely on lymph node number without regard for anatomic classification as in other staging systems [21]. Clearly also the length of bowel resected will dictate how much mesentery accompanies the specimen for evaluation and there is extensive variability in what comprises the ‘standard’. Furthermore, despite a ‘standard’ operation being performed, nodal harvests are often inadequate and many groups currently fall short of the exacting requirements necessary to ensure that the patient is truly node negative [22e24]. Supplementary techniques aimed at increasing lymph harvest are both time- and expense-consuming especially if sophisticated measures of micrometastatic disease are utilized. If validated, an alternative means of performing precise regional staging could in fact aid the standardization of the diagnosis of node negative colon cancer and alleviate much of the variation involved in the analysis of all the nodes present in an entirely resected lymph basin [25].

Appeal of localized resection for colon cancer The potential gains of localized intestinal resection obviously include shortened operative time but also should provide additional benefits arising secondarily from reduced dissection. As much as lessened likelihood of

R.A. Cahill et al. intraoperative haemorrhage, the potential for inadvertent adjacent organ injury is clearly greatly reduced if operative extent is curtailed as the likelihood of ureteric, duodenal and (in the male) spermatic vessel injury is linked to the necessity for root mesenteric dissection. Equally, the hazard of splenic laceration that occurs with mobilization of this left colonic flexure would be obviated in many cases were a limited resection performed as extensive mobilization to ensure a tension-free anastomosis would no longer be necessary. This operative step, rated as considerably hazardous by trainees [26], leads to iatrogenic injury to the spleen in between 1% and 8% of left hemicolectomies and indeed colonic surgery in general accounts for between 34.3% and 59.9% of splenectomies for iatrogenic injury [27e29]. This results in considerable acute morbidity as well as prolonged operation time and hospital stay [30], and the patient engenders both postoperative [31] and life-long [32] infectious susceptibility and, it seems, impaired oncological outcome[33,34]. Postoperatively, bowel function may also be expected to be better with limited field dissection[35,36] as symptoms noticeably deteriorate with increasing length of left colon resection[37] and seem ameliorated when longer remnants have been conserved [38]. Furthermore diminished rates of anastomotic dehiscence (because of reduced ischemic potential of the resection margins [39e41]) as well as shortened duration of postoperative ileus (known to be related to operative extent [42,43]) are speculatively additional advantages that may combine to reduce postoperative convalescence as well as in-hospital stay and expenditure. Finally, flush ligation of the IMA at its origin from the abdominal aorta risks injury of the para-aortic nerves. By this mechanism, anorectal function may be impaired postoperatively (at least up to one year) as may sexual function [44]. Although urinary dysfunction is more likely related to pre-sacral nerve injury, this too may occur when the radical operation for colon cancer involves dissection of and below the colorectal junction. The potential for these sequelae has received most attention in colonic surgery for benign conditions and, in this scenario, has led many experts to advocate more conservative operations in order to improve patient outcome. In the longer postoperative term, the extent of postoperative adhesion formation has long been established as being related to operative extent and limiting the degree of dissection seems likely to at least limit the distribution if not the degree of peritoneal scarring. This in itself could present considerable advantages for patients, surgeons and health care providers [45].

Specific evidence regarding limited colonic operation Although clinical benefit with lesser operation was first presented decades ago [46], the issue has only infrequently been addressed since and there are only few publications directly comparing limited versus radical resection. There has however been one multicentre randomized trial [47] that addressed this issue before the concept of non-radical surgery became unfashionable and the focus switched to ensuring staging adequacy by maximizing lymph node

Localized resection for colon cancer harvest [48]. This study randomly allotted 260 patients (after exclusions for protocol violations) with intraperitoneal left colonic carcinoma to either radical left hemicolectomy (with ligation of the IMA at its origin) or left segmental colectomy (with preservation of the origin of the IMA). While overall early postoperative morbidity was similar (albeit with a non-significant trend towards increased postoperative mortality in the extended resection group), bowel function was significantly better in the group undergoing the more conservative resection. Since then however there have only been three retrospective single centre reports supporting sigmoidectomy in place of more radical operation in carefully selected patients [18,49,50]. There have though been some additional studies that have focused on the specific operative steps that would be eliminated or at least markedly reduced should a more limited bowel resection be performed. Each of these publications has tended to show advantages for both the operator and patient if dissection extent is minimized. One recent study examining the benefits of selective splenic flexure mobilization during open anterior resection, rather than its performance de rigor, confirmed the considerable practical benefit of reduced operative time without incurring increased anastomotic leak rates [51]. In addition, the lesser dissection that is necessary to perform a medialto-lateral vascular approach in the laparoscopic mobilization of the left colon has been found significantly related to reduced operative time and lessened postoperative recovery for both right [52] and left-sided [53] operations. Finally, the beneficial effects of preservation of the inferior marginal artery have also been shown to impart clinical benefit albeit in operation for benign disease [54]. Although further evidential proof is required, in short, the clinical benefits of localized rather then radical colectomy cannot be assumed to be minimal and may in fact be considerable. Any diminution in surgical risk may particularly present significant advantages in vulnerable patients [55] while ensuring their oncological outcome is not compromised [56].

Current means of regional staging colonic cancer without complete mesenteric resection Although nodal burden increases in association with the T-stage of the primary (see Table 1), the majority of patients with T1 or T2 stage disease could potentially be

Table 1 Table illustrating the proportions of patients with lymph node positivity by T-stage of the primary lesion. Early stage

Lymph node involvement

T1 overall (%) sm1 (%) sm2 (%) sm3 (%) T2 Overall (%)

7e15 3e4.2 8e21.3 23e38.5 14.5e43

Incidence figures derived from Refs. [13,14,67,110e114]. Sm denotes the extent of submucosal invasion within the category of T1 disease.

337 treated with localized resection. The key issue though in order to respect oncological providence is that such N0 patients are precisely identified before opting for a nonradical operative address of the primary lesion (e.g. endoscopic resection of the primary). However, preoperative radiological imaging alone for the detection of nodal metastases has remained unsatisfactory for this purpose because most tumor-containing nodes lie below the threshold of these modality’s discriminative capacity (approximately 70% of nodes containing metastases are less than 5 mm in size[57e61],) despite the use of sophisticated techniques and protocols [62]. Their capacity is particularly limited when the main tumor deposit is a micrometastasis as may be expected in the initial stages of lymphatic dissemination associated with early cancers. However, with modifications modalities such as PETeCT scanning may be able to contribute to any patient-selection process by at least out-ruling the proportion with gross nodal metastases [63,64]. Furthermore while endoscopic ultrasound has proven efficacious for T-staging colon cancer, it has been less sensitive in its capacity to N-stage [65,66]. Finally, and despite considerable recent advances[12,14], analysis of surrogate markers of lymphatic invasion in either biopsy specimens or indeed the fully resected specimen, have not been 100% predictive of nodal involvement. The inability of these modalities to truly reflect the metastatic potential of the primary means that endoscopic resection for even the earliest cancers [67] risks either the understaging of systemic disease or the rendering of the effort redundant if formal resection becomes indicated by the full pathology of the resected specimen [13]. Such an occurrence may either mandate second extirpative operation if suspicion of lymphatic dissemination is aroused only after pathological analysis of the primary tumor [68] or, more worryingly, result in suboptimal clinical outcome if the patient remains understaged. Thus formal nodal analysis remains the gold standard for prognosis prediction and adjuvant therapy prescription [13]. Therefore, currently, the only tumors suitable for localized resection are those in whom the risk of lymphatic spread is absolutely minimal. This has led to recommendations that ESD resection should only be performed in the colon for malignant lesions well below its technical capability (i.e. in general T1 submucosal layer (sm)-1 lesions <20 mm in diameter with no adverse prognostic features) [12,69,70].

Sentinel node mapping for minimally invasive staging of early stage disease Sentinel node mapping in general presents a means of gleaning the same information without recourse to full lymph basin resection. However despite broad acceptance in other cancers (including, in principle, gastric cancer [71e73]), consideration of the technique for colonic neoplasia has been framed by its performance via the same means as the definitive operation (i.e. at either open or laparoscopic resection) [74e82]. This means that the operative approach and access are already determined and so concomitant full lymph node dissection is readily enabled without adding extra procedural effort. However, this perspective is considerably altered if the primary is

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Table 2

R.A. Cahill et al.

Summary table of all published reports regarding sentinel node biopsy in colorectal cancer.

First author

Year

Journal

Detection rate

Accuracy rate

Sensitivity rate

False negative rate

Saha Wiese Waters Bilchik Paramo Wood Wood Saha Esser Bendavid Paramo Wood Bilchik Kitagawa Feig Broderick-Villa Tsioulias Nastro Bilchik Cox Bilchik Turner Trocha Veihl Levine Saha Dan Braat Bertoglio Read Patten Bertagnolli Saha Saha Bembenek Codnignola Dahl Bilchik Tuech Saha Kelder Thomas Covarelli Kelder Bianchi Lim Murawa Bembenek Sandrucci Tiffet Faerden Quadros CA

2000 2000 2000 2001 2001 2001 2001 2001 2001 2002 2002 2002 2002 2002 2002 2002 2002 2002 2003 2003 2003 2003 2003 2003 2003 2004 2004 2004 2004 2004 2004 2004 2004 2004 2005 2005 2005 2006 2006 2006 2006 2006 2006 2007 2007 2007 2007 2007 2007 2007 2008 2008

Ann Surg Oncol Arch Pathol Lab Med Am Surg J Clin Oncol Am J Surg Ann Surg Oncol Surg Endosc Ann Surg Oncol Dis Colon Rectum J Surg Oncol Ann Surg Oncol J GastroInt Surg Eur J Cancer Dis Colon Rectum Am J Surg Cancer J Am Surg Tumori Cancer Control Curr Surg J Clin Oncol Archives Path J GastroInt Surg W J Surg J GastroInt Surg Dis Colon Rectum Arch Surg Eur J Surg Oncol J Surg Oncol Dis Colon Rectum Cancer Ann Surg Ann Surg Oncol Semin Oncol W J Surg J Clin Oncol Eur J Surg Oncol Arch Surg Eur J Surg Oncol Am J Surg Scand J Gastroenterol Am Surg Am Surg Int J Col Dis Surg End Ann Surg Oncol Acta Chir Belg Ann Surg J Surg Oncol Dis Colon Rectum Dis Colon Rectum J Surg Oncol

99 99 91 100 71 96 100 98 58 90 82 97 97 91 98 92 100 75 100 100 96 82 98 87 92 99 99 94 95 79 98 92 100 100 85 100 100 100 97 98 97 93 95 97 100 99 93 85 100 92 93 91

96 96 100 100 100 95 100 96 94 94 98 95 95 92 79 79 93 100 93 100 96 92 95 78 ns ns 96 97 92 97 89 80 95 96 ns ns 92 95 94 96 93 20 95 96 95 83 84 86 91 81 86 79.5

91 91 100 100 97 88 100 90 67 95 93 92 91 82 38 50 67 100 91 100 92 87 84 50 50 88 86 80 78 25 83 46 84 92 92 72 83 88 91 90 86 46 86 89 83 59 83 54 92 80 53 65

9 9 0 0 3 12 0 10 33 5 7 8 5 18 62 50 33 0 9 0 8 13 16 22 ns 12 16 20 22 75 17 54 16 8 4 28 17 12 9 10 14 54 14 11 17 41 17 46 9 20 47 35

Note: All studies are shown for completeness, however several studies have published experiences more than once and so have likely overlapped patient cohorts.

Localized resection for colon cancer proposed to be resected by an intraluminal or transluminal endoscopic route. This is particularly the case given that the sentinel node mapping can be performed by a laparoscopic route (and perhaps even by a single port access operation) or, more intriguingly although still experimental, by a N.O.T.E.S. approach [83]. Further, as much as aiding in ensuring appropriate patient selection by regional staging, the presence of a concomitant intraperitoneal view may supplement endoscopic resection of small primary lesions in a role already been proposed for adjoint laparoscopy [84,85]. Thus in this way sentinel node biopsy could augment the oncological providence of endoscopic resective techniques without undermining their clinical appositeness. Confidence in intestinal lymphatic mapping has however been undermined by high discrepancies in the reported results (see Table 2). However, to date, the primary focus has been on the facility of sophisticated histological scrutiny of the sentinel node to upstage disease after conventional operation has taken place and the focus has primarily been on patients with Stage II disease rather than Stage I. Closer analysis of the literature regarding sentinel node in colon cancer reveals that the considerable variability in results may be explained by the considerable heterogeneity of study design employed and, in particular, their patient inclusion criteria [86]. Although selective extraction of data by formal meta-analysis to definitively determine the adequacy of the technique selectively in early stage colon cancer is impossible by reason of lack of homogeneity [87], every analysis of false negative rates to date points to contamination of the study cohort by rectal cancer, inclusion of advanced colonic disease, operator inexperience and patient obesity as primary confounders of the technique. However two large multicentre trials have shown that, when these factors are adjusted for, the accuracy of the technique can approach similar levels to those that justify its use as a means of individualization of surgical resection extent in breast cancer and melanoma (i.e. sensitivity of 95%) [88,89]. Therefore, as in these diseases, it may be that the technique is most reliable in those same patients who are most suitable for localized resection of their primary (i.e. T1 and perhaps T2 disease of small diameter) although this has yet to be definitively proven in a prospective manner. Additionally, the current propensity for performing sentinel node biopsy as an adjunct to conventional staging has led the technique to develop within this conceptual framework. As the operation proceeds regardless, blue dye alone is most often considered sufficient for the mapping. However, the greater import that would be attached to the accuracy and reliability of the technique if operative extent was indeed to be determined by the results of this test would encourage the use and development of additional means of improving technical efficacy and efficiency. Already there have been reports regarding the use of isotype markers (suggested to improve the techniques results for cancers of the colon [90,91] as well as for other sites [92e94]), fluorescent dyes [95,96] and enhanced detection probes [97] (both likely to help in obese mesenteries e a considerable confounding issue in sentinel node detection rates [98]) and further advances would be likely if the clinical indication shifted to require it. One intriguing such

339 possibility would be the harness of advanced optical imaging techniques such as optical coherence tomography [99] with or without spectroscopy [100,101] (among other techniques [102]) to perform an ‘in vivo’ virtual biopsy of the sentinel node in situ. It is clear though that any means of performing rapid analysis of the selected nodes in order to allow the resection to progress by which ever means found appropriate (i.e. endoscopic or conventional) would have to meet or exceed the use of immunohistochemistry in the detection of micrometastases. However there is precedent for such analysis for breast cancer in particular [103e106]. Finally, consideration could be given, at least in the early stages of any clinical experience, to confining the technique to those patients least likely to harbour lymphatic metastases (e.g. screen detected early stage cancer) or those in whom the sentinel node is most likely to be detected (e.g. slim patients without previous abdominal operation). Adjunctive radiological staging as discussed above may also contribute by out-ruling patients with evident lymphadenopathy.

Concluding discussion None of the concepts presented here are particularly new and similar considerations have previously prompted others to look for ways to safely reduce dissection extent by careful case selection [107e109]. Inaccuracy of surrogate markers and concern over non-adjacent or skip metastases remains the main limitation of these proposals however. What makes their reconsideration compelling now is the potential confluence of novel technologies that encourage fundamental challenge of our current preconceptions. Definitive excisional surgery and staging assurance for early stage colon cancer without recourse to conventional operation is certainly possible in concept and seems likely to be increasingly advocated by experts and sought by patients. In the absence of a compelling disruptive technology emerging, lymphatic mapping and sentinel node biopsy seems best placed to provide supportive oncological propriety in the near future. However, it should be stated that, in general, technology is best developed following the clinical indication. Therefore, if localized resection for early stage cancer becomes an acceptable concept, it is likely that current technologies such as radiological staging will be re-directed towards this application and will likely develop to meet its demands. In conclusion however, while intuitively attractive, it remains to be definitively proven that localized resection of early stage colon cancer can meet the oncological requirements of cancer surgery and indeed whether lymphatic mapping can determine regional nodal status as accurately as en bloc mesenteric resection in early stage colon cancer. Any short-term patient benefits they may supply would be markedly outweighed by any compromise of oncological outcome and so progress in this field must be cautiously undertaken with a focus on cancer biology and therapy as much as technological and technical advance.

Conflict of interest statement The authors have no conflict of interest.

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